Splicing Shift of RAC1 Accelerates Tumorigenesis and Defines a Potent Therapeutic Target in Lung Cancer.

ABSTRACT: Dysregulated RNA splicing has emerged as a pervasive yet understudied feature of cancer. The small GTPase RAC1 undergoes splicing changes in multiple cancers. However, the in vivo functional disparities between the two major RAC1 isoforms, RAC1B and the canonical RAC1A, and their therapeutic implications in cancer remain largely unexplored. Here, RAC1B is found to be significantly upregulated in lung adenocarcinoma (LUAD) patients, particularly in those harboring EGFR mutations. Through isoform-specific overexpression and depletion assays in murine and cellular models of EGFR-mutant LUAD, it is revealed that RAC1B, but not RAC1A, promotes LUAD cell proliferation and tumor growth. Mechanistically, RAC1B stabilizes EGFR by inhibiting its lysosome trafficking and degradation. This function is

SUBMITTER: Yan Y 

PROVIDER: S-EPMC12412597 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature